This proposal aims at 1) Investigating the genetic control of collagen production in a variety of cells whose common feature is that they produce an extracellular matrix, and 2) Investigating the collagen-related proteins produced by established cell lines derived from tissues of early embryonic development. 1) To this end we intend to establish cell lines in culture from human or animal origin and investigate the genetic control over collagen synthesis and processing by use of somatic cell hybridization. Isolation and characterization of the procollagens produced by different cell hybrids as well as specific gene mapping of the more than twenty possible genes responsible for procollagen synthesis and processing will enable us to better understand how errors in synthesis or maturation of procollagen are manifested as heritable connective tissue disorders as well as possibly leading to diagnostic procedures for determining that such a disorder exists in the developing fetus. 2) We intend to establish cell lines in culture from teratocarcinomas, blastocysts, and fetuses obtained from normal mice and mice having heritable connective tissue disorders, especially lethal disorders. We will isolate and characterize the collagenous protein produced by these cell lines to determine if different or "new" collagen types exist during early development, when collagen production first appears in developing tissues, whether certain procollagens or collagens influence further tissue development (induction), and to determine the exact lesion in the collagen synthetic pathway responsible for heritable connective tissue disorders in mice that are models for human disorders. These studies will enable us to better understand the role of collagen or procollagen during development as well as to better understand how errors in synthesis or maturation of procollagen are manifested as heritable connective tissue disorders.